Issue
The effect and clinical significance of FN1 expression on biological functions of gastric cancer cells
Corresponding Author(s) : Xinguo Zhu
Cellular and Molecular Biology,
Vol. 66 No. 5: Issue 5
Abstract
Fibronectin 1 (FN1) is a glycoprotein molecule widely distributed in cell structures such as smooth muscle cell layer, vascular cell membrane and nerve cell layer. It participates in cell adhesion, migration and movement of various cells. In recent years, FN1 has been shown to play an important role in the regulation of various malignant tumors such as lung cancer, colorectal cancer, and ovarian cancer. However, its regulation and mechanism of action in gastric cancer have been rarely reported, and these are also associated with some controversy. The aim of this study was to investigate the clinical significance of FN1 in gastric cancer, to study the effects of FN1 on proliferation, apoptosis, migration and invasion of GC cells, and the mechanisms involved. The expression of FN1 in gastric cancer tissues was determined using immunohistochemistry staining. The comparative expression levels of FN1 were assayed with RT-PCR and Western blotting. The correlation amongst FN1 expression, clinicopathological parameters and prognosis of gastric cancer patients was determined. Cell transfection was used to silenceFN1 expression in gastric cancer cells. Plate cloning and CCK-8 assays were used to determine cell proliferation, while apoptosis was assayed with flow cytometry. Cell migration and invasion was measured with transwell assay. The expressions of EMT-related proteins were assayed using western blotting. The results showed that FN1 was upregulated in GC tissues and cell lines, and its expression level was closely related to tumor invasion, TNM stage, lymph node metastasis and survival. Inhibition of FN1 expression significantly reduced proliferation, migration, invasion and EMT processes of GC cells, and enhanced cell apoptosis. These results confirm that FN1 is up-regulated in GC, thereby functioning as an oncogenic gene. The high expression of FN1 might affect the clinicopathological parameters and prognosis of gastric cancer patients.
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- Roberts SE, Morrison-Rees S, Samuel DG, Thorne K, Akbari A, Williams JG. Review article: the prevalence of Helicobacter pylori and the incidence of gastric cancer across Europe. Aliment Pharmacol Ther 2016; 43: 334-345.
- Glasner A, Levi A, Enk J, Isaacson B, Viukov S, Orlanski S, et al. NKp46 receptor-mediated interferon-γ production by natural killer cells increases fibronectin 1 to alter tumor architecture and control metastasis. Immunity 2018; 48: 107-119.
- Kim H, Park J, Kim Y, Sohn A, Yeo I, Jong Yu S, et al. Serum fibronectin distinguishes the early stages of hepatocellular carcinoma. Sci Rep 2017; 7: 9449.
- Žlajpah M, Hauptman N, Boštjanćić E, Zidar N. Differential expression of extracellular matrix"‘related genes DCN, EPHA4, FN1, SPARC, SPON2 and SPP1 in colorectal carcinogenesis. Oncol Rep 2019; 42: 1539-1548.
- Cohen C, Leal MF, Belangero PS, Figueiredo EA, Smith MC, Andreoli CV, et al. The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study. Clinics 2016; 71: 325-331.
- Zhang H, Sun Z, Li Y, Fan D, Jiang H. MicroRNA-200c binding to FN1 suppresses the proliferation, migration and invasion of gastric cancer cells. Biomed Pharmacother 2017; 88: 285-292.
- Goto O, Takeuchi H, Kitagawa Y, Yahagi N. Hybrid surgery for early gastric cancer. Transl Gastroenterol Hepatol 2016; 1: 26.
- Jiang K, Liu H, Xie D, Xiao Q. Differentially expressed genes ASPN, COL1A1, FN1, VCAN and MUC5AC are potential prognostic biomarkers for gastric cancer. Oncol Lett 2019; 17: 3191-3202.
- Lee JC, Su SY, Changou CA, Yang RS, Tsai KS, Collins MT, et al. Characterization of FN1–FGFR1 and novel FN1–FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors. Mod Pathol 2016; 29: 1335.
- Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Ogino S, et al. Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells. Oncotarget 2016; 7: 56855.
- Cai X, Liu C, Zhang TN, Zhu YW, Dong X, Xue P. Down-regulation of FN1 inhibits colorectal carcinogenesis by suppressing proliferation, migration, and invasion. J Cell Biochem 2018; 119: 4717-4728.
- Kondisetty S, Menon KN, Pooleri GK. Fibronectin protein expression in renal cell carcinoma in correlation with clinical stage of tumour. Biomark Res 2018; 6: 23.
- Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Clin Exp Metastasis 2016; 33: 29-44.
- Zhou Y, Shu C, Huang Y. Fibronectin promotes cervical cancer tumorigenesis through activating FAK signaling pathway. J Cell Biochem 2019; 120: 10988-10997.
- Liang H, Yu M, Yang R, Zhang L, Zhang L, Zhu D, et al. A PTAL-miR-101-FN1 Axis Promotes EMT and Invasion-Metastasis in Serous Ovarian Cancer. Mol Ther Oncolytics 2019; 16: 53-62.
- Zhang J, Yan Y, Yang Y, Wang L, Li M, Wang J, et al. High infiltration of tumor-associated macrophages influences poor prognosis in human gastric cancer patients, associates with the phenomenon of EMT. Medicine 2016; 95: 2636.
- Cui D, Zhang C, Liu B, Shu Y, Du T, Shu D, et al. Regression of gastric cancer by systemic injection of RNA nanoparticles carrying both ligand and siRNA. Sci Rep 2015; 5: 10726.
- Li BP, Liu JL, Chen JQ, Wang Z, Mao YT, Chen YY. Effects of siRNA-mediated silencing of myeloid cell leukelia-1 on the biological behaviors and drug resistance of gastric cancer cells. Am J Transl Res 2015; 7: 2397.
- Chen SZ, Yao HQ, Zhu SZ, Li QY, Guo GH, Yu J. Expression levels of matrix metalloproteinase-9 in human gastric carcinoma. Oncol Lett 2015; 9: 915-919.
- Li W, Li S, Deng L, Yang S, Li M, Long S, et al. Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT. Tumor Biol 2015; 36: 6883-6889.
References
Roberts SE, Morrison-Rees S, Samuel DG, Thorne K, Akbari A, Williams JG. Review article: the prevalence of Helicobacter pylori and the incidence of gastric cancer across Europe. Aliment Pharmacol Ther 2016; 43: 334-345.
Glasner A, Levi A, Enk J, Isaacson B, Viukov S, Orlanski S, et al. NKp46 receptor-mediated interferon-γ production by natural killer cells increases fibronectin 1 to alter tumor architecture and control metastasis. Immunity 2018; 48: 107-119.
Kim H, Park J, Kim Y, Sohn A, Yeo I, Jong Yu S, et al. Serum fibronectin distinguishes the early stages of hepatocellular carcinoma. Sci Rep 2017; 7: 9449.
Žlajpah M, Hauptman N, Boštjanćić E, Zidar N. Differential expression of extracellular matrix"‘related genes DCN, EPHA4, FN1, SPARC, SPON2 and SPP1 in colorectal carcinogenesis. Oncol Rep 2019; 42: 1539-1548.
Cohen C, Leal MF, Belangero PS, Figueiredo EA, Smith MC, Andreoli CV, et al. The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study. Clinics 2016; 71: 325-331.
Zhang H, Sun Z, Li Y, Fan D, Jiang H. MicroRNA-200c binding to FN1 suppresses the proliferation, migration and invasion of gastric cancer cells. Biomed Pharmacother 2017; 88: 285-292.
Goto O, Takeuchi H, Kitagawa Y, Yahagi N. Hybrid surgery for early gastric cancer. Transl Gastroenterol Hepatol 2016; 1: 26.
Jiang K, Liu H, Xie D, Xiao Q. Differentially expressed genes ASPN, COL1A1, FN1, VCAN and MUC5AC are potential prognostic biomarkers for gastric cancer. Oncol Lett 2019; 17: 3191-3202.
Lee JC, Su SY, Changou CA, Yang RS, Tsai KS, Collins MT, et al. Characterization of FN1–FGFR1 and novel FN1–FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors. Mod Pathol 2016; 29: 1335.
Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Ogino S, et al. Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells. Oncotarget 2016; 7: 56855.
Cai X, Liu C, Zhang TN, Zhu YW, Dong X, Xue P. Down-regulation of FN1 inhibits colorectal carcinogenesis by suppressing proliferation, migration, and invasion. J Cell Biochem 2018; 119: 4717-4728.
Kondisetty S, Menon KN, Pooleri GK. Fibronectin protein expression in renal cell carcinoma in correlation with clinical stage of tumour. Biomark Res 2018; 6: 23.
Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Clin Exp Metastasis 2016; 33: 29-44.
Zhou Y, Shu C, Huang Y. Fibronectin promotes cervical cancer tumorigenesis through activating FAK signaling pathway. J Cell Biochem 2019; 120: 10988-10997.
Liang H, Yu M, Yang R, Zhang L, Zhang L, Zhu D, et al. A PTAL-miR-101-FN1 Axis Promotes EMT and Invasion-Metastasis in Serous Ovarian Cancer. Mol Ther Oncolytics 2019; 16: 53-62.
Zhang J, Yan Y, Yang Y, Wang L, Li M, Wang J, et al. High infiltration of tumor-associated macrophages influences poor prognosis in human gastric cancer patients, associates with the phenomenon of EMT. Medicine 2016; 95: 2636.
Cui D, Zhang C, Liu B, Shu Y, Du T, Shu D, et al. Regression of gastric cancer by systemic injection of RNA nanoparticles carrying both ligand and siRNA. Sci Rep 2015; 5: 10726.
Li BP, Liu JL, Chen JQ, Wang Z, Mao YT, Chen YY. Effects of siRNA-mediated silencing of myeloid cell leukelia-1 on the biological behaviors and drug resistance of gastric cancer cells. Am J Transl Res 2015; 7: 2397.
Chen SZ, Yao HQ, Zhu SZ, Li QY, Guo GH, Yu J. Expression levels of matrix metalloproteinase-9 in human gastric carcinoma. Oncol Lett 2015; 9: 915-919.
Li W, Li S, Deng L, Yang S, Li M, Long S, et al. Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT. Tumor Biol 2015; 36: 6883-6889.